EP2144620B1 - Neuartiges verfahren zur herstellung gereinigter extrakte aus harpagophytum procumbens - Google Patents

Neuartiges verfahren zur herstellung gereinigter extrakte aus harpagophytum procumbens Download PDF

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Publication number
EP2144620B1
EP2144620B1 EP08805723.7A EP08805723A EP2144620B1 EP 2144620 B1 EP2144620 B1 EP 2144620B1 EP 08805723 A EP08805723 A EP 08805723A EP 2144620 B1 EP2144620 B1 EP 2144620B1
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Prior art keywords
liquid
harpagoside
extract
harpagophytum procumbens
concentrated
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EP08805723.7A
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English (en)
French (fr)
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EP2144620A2 (de
Inventor
Yohan Rolland
Charles Duval
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Givaudan France Naturals SAS
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Naturex SA
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a process for preparing purified extracts of Harpagophytum procumbens, said extracts being in liquid or dry form.
  • the present invention also relates to purified extracts as obtained by said process.
  • Harpagophytum ( Harpagophytum procumbens ) is a plant native to South Africa, traditionally known for its effectiveness in the treatment, among others, osteoarthritis pain.
  • Tuberous secondary roots contain in particular compounds of the iridoids type, glycosylated or not, considered as the active ingredients, called harpagoside, harpagide, procumbide and procumboside.
  • the harpagophytum extracts are usually obtained using hydro-alcoholic solvents, the alcoholic content can vary from 0 (water extract) to 90% ( Chrubasik S.; Devil's claw extract as an example of the effectiveness of herbal analgesics; Orthopäde. 2004 Jul; 33 (7): 804-8 ).
  • the European Pharmacopoeia also describes in the monograph of the harpagophytum root the use of methanol for the extraction of harpagoside.
  • the plant is separated from the extraction solvent by all the usual methods, for example filtration or centrifugation.
  • the filtrate is desolventized in the case of the use of alcoholic solvent, optionally concentrated to reduce the volume, and then dried.
  • Carbon dioxide / modified solvent extracts of Harpagophytum procumbens roots were studied for extraction efficiency and harpagoside content, and compared to a conventional extract.
  • the effects of pressure, temperature, type and modifier concentration were examined. Two extraction steps were necessary to obtain anti-inflammatory extracts strongly enriched with harpagoside.
  • the first extraction step was carried out in the supercritical state using carbon dioxide modified with n-propanol to remove undesired lipophilic substances.
  • the main extraction was performed in the supercritical or subcritical state with carbon dioxide modified with ethanol.
  • Supercritical liquid extraction resulted in extracts containing harpagoside up to more than 30%.
  • the subcritical extracts showed a harpagoside content of 20%, but the extraction yield was almost three times greater than under supercritical conditions.
  • the harpagoside recovery rate resulting from the sum of the extract and the crude residue was 99% greater than in all previous experiments.
  • the conventional extract and two carbon dioxide extracts were examined for in vitro inhibition of lipoxygenase 5 or cyclooxygenase-2 biosynthesis.
  • the two carbon dioxide extracts showed total inhibition on the biosynthesis of lipoxygenase 5 at a concentration of 51.8 mg / l; on the other hand, the conventional extract does not show inhibition of lipoxygenase 5 biosynthesis.
  • the products obtained by the extractions with CO 2 are generally not in powder, but rather in the form of paste or wax, which is not compatible with the manufacture of capsules for example, or else possibly adsorbed on a support, this which decreases the title of the product. Moreover, the products thus obtained are liposoluble extracts and therefore not soluble in the aqueous phases. Finally, it can be pointed out that this type of process using CO 2 results in pesticides and mycotoxin-type compounds, so they concentrate them in the finished product. Thus, the CO 2 extractions do not make it possible to obtain harpagophytum extracts having a high harpagoside titre compatible with all the liquid or dry galenic formulations.
  • the object of the present invention is to provide an industrially applicable preparation process for purified harpagophytum extracts having a high harpagoside titre, said extracts thus obtained being compatible with all liquid galenics (syrups or capsules) or dry (tablets or capsules).
  • the present invention relates to a process for preparing a concentrated extract of Harpagophytum procumbens, in liquid or dry form, with a harpagoside titer greater than or equal to 5%, preferably greater than or equal to 35%, comprising a purification step of a crude extract of Harpagophytum procumbens in liquid form in aqueous phase, by a liquid-liquid extraction technique with an organic solvent chosen from esters, especially aliphatic esters, and more particularly from alkyl acetates, said alkyl group being an alkylated, branched or linear chain comprising from 1 to 10, in particular from 1 to 6, and preferably from 1 to 4 carbon atoms.
  • the present invention is based on the fact that the inventors have found that the iridoid glucosides of harpagophytum can be surprisingly purified using ester type solvents.
  • esters such as ethyl acetate
  • the esters are very selective with respect to this type of compound, and allow very efficient purifications up to titres greater than 35% on a dry basis.
  • esters whose boiling point is lower than that of the alcohols used in the state of the art makes it possible not to expose the product (active principle - harpagoside) to high temperatures. which reduces the duration of the process exposing the product to high temperatures.
  • the thermal degradations of the active principles then do not take place and it is thus possible to maintain high titers on the purified extracts obtained (up to at least 35%).
  • Lyophilization can be a drying means used for example.
  • the harpagoside titre mentioned above is a weight / weight (w / w) weight relative to the total weight of solids.
  • control solution 1 mg of harpagoside in 1 ml of methanol
  • control solution 1 mg of harpagoside in 1 ml of methanol
  • Chromatographic analysis the test solution is injected and the sensitivity of the system is adjusted so that the height of the peak corresponding to methyl cinnamate represents 50% of the total scale of the recorder.
  • the concentrated organic phase harpagoside preferably has a harpagoside titer greater than or equal to 5%.
  • the organic solvent used as part of the purification step by a liquid-liquid extraction technique is chosen from esters, especially aliphatic esters, and more particularly from acetates.
  • esters especially aliphatic esters, and more particularly from acetates.
  • the organic solvent used for the liquid-liquid extraction step is methyl acetate, ethyl acetate and butyl acetate.
  • Ethyl acetate is particularly preferred because it is the most common industrially, has a very low boiling point (77.06 ° C) and is a food solvent.
  • ethyl acetate has the advantage of being a water-immiscible solvent authorized for use in food which makes it possible to purify the extracts of harpagophytum and to attain titres greater than or equal to 35%.
  • ethyl acetate makes it possible to carry out the evaporation-drying operations at a much lower temperature than when, for example, butanol is used. This reduction in temperature then makes it possible to limit the degradation of the active ingredients.
  • ethyl acetate (boiling point 77 ° C at atmospheric pressure) and water form an azeotrope which boils at 70.4 ° C at atmospheric pressure, and at less than 40 ° C under a vacuum. 0.1 bar.
  • the water-butanol azeotrope contains 42.4% of water, whereas the water-ethyl acetate azeotrope contains only 8.5% of water, which allows its industrial recycling for new purifications without additional treatment.
  • the equipment used is of any type allowing the mixing of two liquids, more particularly agitated reactor or packed column and in particular centrifugal type, equipment that allows to harvest quickly the two phases of the process: the concentrated aqueous phase, exhausted in harpagoside, and the organic phase loaded with harpagoside. This process makes it possible to recover more than 90% of the active ingredients present in the starting aqueous phase.
  • the present invention also relates to a process as defined above, characterized in that the crude extract of Harpagophytum procumbens is obtained by a process comprising a step of bringing into contact a solvent of hydro-alcoholic type constituted up to at 90% alcohol with dried secondary roots of Harpagophytum procumbens, and in particular by extraction, maceration, decoction or percolation, a solvent removal step by solid / liquid separation, in particular by filtration, by desolventization or by centrifugation for recovering said crude extract and a possible concentration step of said crude extract in order to obtain said crude extract in the form of a thick liquid containing from 2 to 50% solids.
  • the aforementioned alcohol constituting the hydroalcoholic solvent is methanol or ethanol.
  • the present invention also relates to a process as defined above, in which the transformation of the concentrated extract in liquid form by physical or physicochemical means is carried out by removing the water in a hot air flow, by drying, by nebulization, by evaporation, by sublimation, by dehydration, by adsorption on a support.
  • the present invention also relates to the extracts as obtained by the implementation of the method of the invention as defined above.
  • the present invention relates to a concentrated extract of Harpagophytum procumbens, in liquid form, soluble in aqueous phase, with a harpagoside titer of greater than or equal to 35%, preferably of 35% to 50%, especially 35% to 45% and preferably from 35% to 40%.
  • the present invention also relates to a concentrated extract of Harpagophytum procumbens, in dry form, with a harpagoside titer of greater than or equal to 35%, preferably of 35% at 50%, especially 35% to about 45%, and preferably 35% to 40%.
  • the present invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising as active substance a concentrated extract of Harpagophytum procumbens, in liquid or dry form, in association with a pharmaceutically acceptable vehicle.
  • the present invention also relates to a dietary supplement comprising a concentrated extract of Harpagophytum procumbens, in liquid or dry form, in association with an acceptable vehicle.
  • the raw extract is prepared from a ton of harpagophytum secondary roots. These secondary roots are macerated in water, with stirring, for 2 hours. Then, a separation step is carried out between the plant and the solvent by successive filtrations (600 ⁇ m, 100 ⁇ m, then 25 ⁇ m). The next step is a vacuum concentration step which eliminates even more solvent and avoids handling too much solvent afterwards.
  • the concentrate is directly extracted in the liquid phase with 1000 L of ethyl acetate using a continuous centrifugal extractor.
  • the organic phase is recovered and desolventized under vacuum.
  • An aqueous phase concentrate is obtained which can be reduced to powder, for example in a stirred reactor under vacuum.
  • the crude extract is prepared from one kg of harpagophytum secondary roots. These secondary roots are macerated in ethanol (70% vol.) At 65 ° C., with stirring, for 2 hours. Then, a separation step is carried out between the plant and the solvent by successive filtrations (600 ⁇ m, 100 ⁇ m, then 25 ⁇ m). The next step is a step concentration of vacuum which eliminates even more solvent and avoids handling too much solvent afterwards.
  • the concentrate is directly extracted in the liquid phase with 1000 mL of ethyl acetate using a continuous centrifugal extractor (at 0 ° C).
  • the organic phase is recovered and desolventized under vacuum.
  • aqueous phase concentrate is obtained which can be reduced to powder, for example by lyophilization.
  • a powder (20 g) is obtained.
  • the product obtained has a 55% harpagoside content as measured by HPLC.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
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  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Saccharide Compounds (AREA)
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  • Steroid Compounds (AREA)

Claims (10)

  1. Verfahren zur Herstellung eines konzentrierten Extrakts aus Harpagophytum procumbens, in flüssiger oder trockener Form, mit einem Harpagosid Titer größer als oder gleich 5%, umfassend einen Schritt der Reinigung eines rohen Extrakts aus Harpagophytum procumbens in flüssiger Form aus der flüssigen Phase durch eine Technik der Flüssig-Flüssig-Extraktion mit einem organischen Lösungsmittel ausgewählt unter den Estern, vorzugsweise den aliphatischen Estern und weiter bevorzugt aus Alkylacetaten.
  2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass das organische Lösungsmittel ein Alkylacetat ist.
  3. Verfahren nach Anspruch 1 oder 2, umfassend die folgenden Schritte:
    - einen Reinigungsschritt des Typs der Flüssig-Flüssig-Extraktion zwischen einem rohen Extrakts aus Harpagophytum procumbens in flüssiger Form aus der flüssigen Phase und einem organischen Lösungsmittel ausgewählt unter den Estern um eine flüssige Phase und eine konzentrierte organische Phase Harpagosid,
    - einen Schritt der Beseitigung des Lösungsmittels ab der zuvor gewonnenen organischen Phase, um das genannte Extrakt in konzentrierter flüssiger Form zu erhalten und
    - einen eventuellen Schritt der Transformation des genannten konzentrierten Extrakts in der flüssigen Phase durch physikalische oder physikalischchemische Mittel, um einen konzentrierten Extrakt in trockener Form zu erhalten.
  4. Verfahren nach einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass das rohe Extrakt aus Harpagophytum procumbens, das zur Durchführung des Reinigungsschrittes verwendet wurde, durch ein Verfahren, umfassen einen Schritt des In-Kontaktbringens mit einem Wasser-Alkohol-Lösemitteltyp, der bis zu 90% Alkohol umfasst mit trockenen sekundären Wurzeln aus Harpagophytum procumbens und insbesondere durch Extraktion, Mazeration, Auskochen oder Perkolationsverfahren erhalten wurde, und einen Schritt der Beseitigung des Lösemittels durch eine fest/flüssig Separation, insbesondere durch Filtern, durch Lösemittelentfernung oder durch Zentrifugieren um das genannte rohe Extrakt zurückzugewinnen und einen eventuellen Schritt der Konzentrierung des genannten rohen Extrakts, um das genannte rohe Extrakt in einer flüssigen Form umfassend 2 bis 20% Trockenmasse zu gewinnen.
  5. Verfahren nach Anspruch 4, dadurch gekennzeichnet, dass der Alkohol, der das Lösungsmittel vom Typ der Flüssig-Alkohole umfasst, Methanol oder Ethanol ist.
  6. Verfahren nach einem der Ansprüche 1 bis 5, wobei die Transformation des konzentrierten Extrakts in flüssige Form durch physikalische oder physikalisch-chemische Mittel durch Beseitigung des Wassers in einem warmen Luftstrom, durch Trocknung, durch Vernebelung, durch Verdunstung, durch Sublimation, durch Dehydration oder durch bekannte Adsorptionsverfahren bewirkt wird.
  7. Konzentriertes Extrakt aus Harpagophytum procumbens, in flüssiger Form, mit einem Harpagosid Titer größer als oder gleich 5%, vorzugsweise von 35% bis 50%, insbesondere von 35% bis 45% und bevorzugt von 35% bis 40%.
  8. Konzentriertes Extrakt aus Harpagophytum procumbens, in trockener Form, mit einem Harpagosid Titer größer als oder gleich 5%, vorzugsweise von 35% bis 50%, insbesondere von 35% bis 45% und bevorzugt von 35% bis 40%.
  9. Pharmazeutische Zusammensetzung enthaltend einen konzentrierten Wirkstoff aus Harpagophytum procumbens gemäß dem Anspruch 7 oder 8 in Verbindung mit einem pharmazeutisch aufnehmbaren Träger.
  10. Nahrungsergänzungsmittel enthaltend einen konzentrierten Wirkstoff aus Harpagophytum procumbens gemäß dem Anspruch 7 oder 8 in Verbindung mit einem aufnehmbaren Träger.
EP08805723.7A 2007-05-07 2008-04-28 Neuartiges verfahren zur herstellung gereinigter extrakte aus harpagophytum procumbens Active EP2144620B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0754906A FR2915900B1 (fr) 2007-05-07 2007-05-07 Nouveau procede de preparation d'extraits purifies d'harpagophytum procumbens.
PCT/FR2008/050769 WO2008145931A2 (fr) 2007-05-07 2008-04-28 Nouveau procede de preparation d'extraits purifies d'harpagophytum procumbens

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EP2144620A2 EP2144620A2 (de) 2010-01-20
EP2144620B1 true EP2144620B1 (de) 2015-10-21

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US (2) US10111917B2 (de)
EP (1) EP2144620B1 (de)
DK (1) DK2144620T3 (de)
ES (1) ES2559863T3 (de)
FR (1) FR2915900B1 (de)
WO (1) WO2008145931A2 (de)

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Publication number Priority date Publication date Assignee Title
FR2961401B1 (fr) 2010-06-17 2013-04-05 Laetitia Mathez Composition anti-inflammatoire
FR2968215B1 (fr) 2010-12-02 2013-08-23 Laetitia Mathez Composition comprenant un element chondroprotecteur et des vitamines
ITRM20130501A1 (it) * 2013-09-10 2015-03-11 Aboca Spa Societa Agricola Nuovi estratti di artiglio del diavolo e loro usi.
CN104833763B (zh) * 2015-05-07 2017-03-15 河南省康星药业股份有限公司 参草超微粉中哈巴俄苷的鉴别方法
CN110412155B (zh) * 2019-07-03 2022-02-25 东阿阿胶股份有限公司 一种两地汤的hplc特征图谱的检测方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR920005686B1 (ko) 1989-11-07 1992-07-13 동국제약 주식회사 하르파고시드 함유 엑기스의 추출방법
DE19603788B4 (de) * 1996-02-02 2005-12-22 Chrubasik, Sigrun, Dr. Wirkstoffextrakt aus Teufelskrallenwurzel, diesen enthaltendes human- oder veterinärmedizinisches Präparat, Verfahren zur Herstellung eines hochkonzentrierten Extraktes aus Radix Harpagophyti oder Herba und Radix Scrophularia sowie dessen Verwendung
DE19651290A1 (de) * 1996-03-21 1997-10-02 Schwabe Willmar Gmbh & Co Harpagosid-angereicherter Extrakt aus Harpagophytum procumbens und Verfahren zu seiner Herstellung
AU2633297A (en) * 1996-03-21 1997-10-10 Dr. Willmar Schwabe Gmbh & Co Harpagoside-enriched extract from harpagophytum procumbens and processes for producing same
CN1082820C (zh) * 1996-05-18 2002-04-17 芬泽尔伯格股份有限两合公司 钩果草和(或)Harpagophytum zeyheri DENCE的纯化提取物,其制备方法及用途
GB2335919A (en) * 1998-04-01 1999-10-06 Essential Nutrition Ltd A method of producing high anti-inflammatory activity extracts from harpagophytum procumbens
US6197307B1 (en) * 1999-03-30 2001-03-06 Essential Nutrition, Ltd. Method for producing high activity extracts from harpagophytum procumbens
KR100415826B1 (ko) * 2000-11-28 2004-01-31 신준식 구척 및 천수근을 주성분으로 함유하는 약학적 제제
KR100416842B1 (ko) 2000-11-29 2004-02-05 신준식 하르파지드관련 화합물을 유효성분으로 함유하는 골다공증 예방과 치료용 약학적 조성물
EP1371372A1 (de) * 2002-06-08 2003-12-17 Cognis Iberia, S.L. Verwendung von Wirkstoffgemischen enthaltend Tocopherole und Extrakte des Harpagophytum procumbens zur Herstellung eines Medikamentes gegen rheumatische Arthritis
DE10310267A1 (de) * 2003-03-10 2004-09-23 Anoxymer Gmbh Verfahren unter Anwendung von Druck zur intramolekularen Umesterung von cyclischen, mehrfach hydroxylierten Verbindungen

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Publication number Publication date
DK2144620T3 (da) 2016-01-25
EP2144620A2 (de) 2010-01-20
FR2915900B1 (fr) 2012-08-24
US20190022159A1 (en) 2019-01-24
US20100311675A1 (en) 2010-12-09
WO2008145931A3 (fr) 2009-01-29
ES2559863T3 (es) 2016-02-16
FR2915900A1 (fr) 2008-11-14
US10111917B2 (en) 2018-10-30
WO2008145931A2 (fr) 2008-12-04

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